We have developed methods for generating novel nonproducer mouse/human "heteromyelomas" and have produced a series of such clones, each retaining one or more human chromosomes in addition to a major complement of mouse chromosomes. Certain of the clones selected for testing as malignant fusion partners in fusions with antigen-primed human B lymphocytes have already shown the capacity to provide high yields of viable hybridomas, a high proportion of which secrete monoclonal human immunoglobulins that are not diluted or permuted with human or mouse myeloma heavy or light chains. Limited testing indicates stability of secretion by such hybridomas for periods up to at least 6 months. Preliminary tests suggest that in vivo transplantation in the peritoneal cavities of immunosuppressed mice may be feasible. We wish to extend these preliminary studies to include: (1)\test fusions of existing, as yet untested heteromyeloma clones; (2)\generation and testing of additional heteromyelomas retaining more human chromosomes; (3)\generation and testing of "heteromyelolymphomas," involving fusion of a mutant mouse myeloma line with selected, rapidly growing human B-\or null cell lymphomas; (4)\generation and testing of human "myelolymphomas," involving fusion of a mutant human myeloma line with selected, rapidly growing human B-\or null cell lymphomas; (5)\clonal expansion of human B-lymphocytes after optimized priming with antigen in vitro; (6)\development of methods for direct selection and cloning in the cell sorter of heterokaryons resulting from the fusion of cells whose nuclei have been differentially labeled with different fluorochrome dyes; (7)\optimization of conditions for the immunosuppression of mice and/or rats for in vivo passage of producer hybridomas in ascites form; and (8)\studies of the correlation (if any) between karyotype (numbers of mouse versus human chromosomes retained, specific human chromosomes) and efficiency of hybrids as malignant fusion partners. (2)